Interactions between glial cells and the blood-brain barrier and their role in Alzheimer's disease

Zhao, Ming; Jiang, Xuefan; Zhang, Huiqin; Sun, Jiahui; Peng, Hui; Ma, Lina; Cao, Yu; Li, Hao

doi:10.1016/j.arr.2021.101483

Cited by 46 publications

(33 citation statements)

References 176 publications

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“…Astrocytes contribute to the clearance of Aβ by expressing Aβ-degrading enzymes and related receptors, and microglia are involved in phagocytosis in the normal brain ( Apatiga-Perez et al, 2021 ). However, under pathological conditions, these cells are overactivated, causing inflammation and increasing the deposition of Aβ ( Kwon and Koh, 2020 ; Zhao et al, 2021 ). In the cerebrovascular system, the transporter LRP1 passes through the blood-brain barrier to transport Aβ from around blood vessels to the circulating blood, thus participating in the clearance of Aβ ( Deane et al, 2004 ; Iadecola, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

“…In APP/PS1 mice, there were a large number of GFAP-positive cells and blood vessels around Aβ peptides in the cortex and hippocampus, implying a close connection between astrocytes and blood vessels ( Figure 8 ). Astrocytes and neurons wrap brain capillary endothelial cells to form the blood-brain barrier, which is the main mechanism through which Aβ is cleared ( Zhao et al, 2021 ). In AD, the characteristic of the impaired blood-brain barrier has been widely reported ( Kirabali et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…Under normal circumstances, astrocytes release specific protective factors, including vascular endothelial growth factor (VEGF), insulin-like growth factor-1, glial cell-derived neurotrophic factor and angiopoietin-1, to maintain normal blood-brain barrier function. However, under pathological conditions, such as Aβ stimulation, reactive astrocytes secrete vascular permeability factors and proinflammatory factors, including matrix metalloproteinase-9, nitric oxide, apolipoprotein E-4, interleukin-6, and tumor necrosis factor-α, which aggravate or cause blood-brain barrier damage and inflammation ( Abbott et al, 2006 ; Apatiga-Perez et al, 2021 ; Zhao et al, 2021 ). Our study showed that tDCS reduced astrocyte levels and improved blood-brain barrier function ( Figures 3 – 6 ).…”

Section: Discussionmentioning

confidence: 99%

“…Astrocytes are interconnected with cerebral blood vessels and neurons ( Price et al, 2021 ), which can promote the uptake and synthesis of neurotransmitters, induce angiogenesis and regulate cerebral blood flow, thus contributing to neuroprotection and repair of damaged tissues ( Abbott et al, 2006 ; Sofroniew and Vinters, 2010 ). However, in AD, reactive astrocytes may also secrete vascular permeability factors to destroy the blood-brain barrier, produce proinflammatory factors to cause neuroinflammation and induce an inflammatory cascade, impair Aβ clearance, and ultimately aggravate Aβ accumulation and neuronal degeneration ( Bush et al, 1999 ; Zhao et al, 2021 ). A recent study found that the integrity of blood vessels can be maintained in the absence of astrocyte endfeet ( Kubotera et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

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Transcranial Direct Current Stimulation Alleviates Neurovascular Unit Dysfunction in Mice With Preclinical Alzheimer’s Disease

Luo

Yang

Yan

et al. 2022

Front. Aging Neurosci.

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Neurons, glial cells and blood vessels are collectively referred to as the neurovascular unit (NVU). In the Alzheimer’s disease (AD) brain, the main components of the NVU undergo pathological changes. Transcranial direct current stimulation (tDCS) can protect neurons, induce changes in glial cells, regulate cerebral blood flow, and exert long-term neuroprotection. However, the mechanism by which tDCS improves NVU function is unclear. In this study, we explored the effect of tDCS on the NVU in mice with preclinical AD and the related mechanisms. 10 sessions of tDCS were given to six-month-old male APP/PS1 mice in the preclinical stage. The model group, sham stimulation group, and control group were made up of APP/PS1 mice and C57 mice of the same age. All mice were histologically evaluated two months after receiving tDCS. Protein content was measured using Western blotting and an enzyme-linked immunosorbent assay (ELISA). The link between glial cells and blood vessels was studied using immunofluorescence staining and lectin staining. The results showed that tDCS affected the metabolism of Aβ; the levels of Aβ, amyloid precursor protein (APP) and BACE1 were significantly reduced, and the levels of ADAM10 were significantly increased in the frontal cortex and hippocampus in the stimulation group. In the stimulation group, tDCS reduced the protein levels of Iba1 and GFAP and increased the protein levels of NeuN, LRP1 and PDGRFβ. This suggests that tDCS can improve NVU function in APP/PS1 mice in the preclinical stage. Increased blood vessel density and blood vessel length, decreased IgG extravasation, and increased the protein levels of occludin and coverage of astrocyte foot processes with blood vessels suggested that tDCS had a protective effect on the blood-brain barrier. Furthermore, the increased numbers of Vimentin, S100 expression and blood vessels (lectin-positive) around Aβ indicated that the effect of tDCS was mediated by astrocytes and blood vessels. There was no significant difference in these parameters between the model group and the sham stimulation group. In conclusion, our results show that tDCS can improve NVU function in APP/PS1 mice in the preclinical stage, providing further support for the use of tDCS as a treatment for AD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Transcranial Direct Current Stimulation Alleviates Neurovascular Unit Dysfunction in Mice With Preclinical Alzheimer’s Disease

Luo

Yang

Yan

et al. 2022

Front. Aging Neurosci.

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show abstract

“…The accumulation of Aβ peptide, a major phenomenon in this pathology, induces the accumulation of reactive astrocytes. Thus, reactive astrocytes secrete factors promoting endothelial proliferation, such as VEGF, but also induce the expression of MMPs, thus altering the integrity of the BBB [ 160 ]. The loss or modification of cell–cell communication between astrocyte and BPs leads to the activation of cyclophilin-A in BPs, which promotes MMP9 expression.…”

Section: Maintenance Of the Bbb Phenotype Through Cell–cell Communicationsmentioning

confidence: 99%

The Blood–Brain Barrier, an Evolving Concept Based on Technological Advances and Cell–Cell Communications

Menaceur

Gosselet

Fénart

et al. 2021

Cells

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The construction of the blood–brain barrier (BBB), which is a natural barrier for maintaining brain homeostasis, is the result of a meticulous organisation in space and time of cell–cell communication processes between the endothelial cells that carry the BBB phenotype, the brain pericytes, the glial cells (mainly the astrocytes), and the neurons. The importance of these communications for the establishment, maturation and maintenance of this unique phenotype had already been suggested in the pioneering work to identify and demonstrate the BBB. As for the history of the BBB, the evolution of analytical techniques has allowed knowledge to evolve on the cell–cell communication pathways involved, as well as on the role played by the cells constituting the neurovascular unit in the maintenance of the BBB phenotype, and more particularly the brain pericytes. This review summarises the key points of the history of the BBB, from its origin to the current knowledge of its physiology, as well as the cell–cell communication pathways identified so far during its development, maintenance, and pathophysiological alteration.

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Role of Stem Cells as a Protective Agent against Neurological Complications

Nayeem,

Ahmed,

Kumar

et al. 2023

Applications of Stem Cells and Derived Exosomes in Neurodegenerative Disorders

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Interactions between glial cells and the blood-brain barrier and their role in Alzheimer's disease

Cited by 46 publications

References 176 publications

Transcranial Direct Current Stimulation Alleviates Neurovascular Unit Dysfunction in Mice With Preclinical Alzheimer’s Disease

Transcranial Direct Current Stimulation Alleviates Neurovascular Unit Dysfunction in Mice With Preclinical Alzheimer’s Disease

The Blood–Brain Barrier, an Evolving Concept Based on Technological Advances and Cell–Cell Communications

Role of Stem Cells as a Protective Agent against Neurological Complications

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